Nitroglycerin is a drug that has been administered as a prompt-acting vasodilator in the relief and treatment of angina pectoris. Nitroglycerin has also been used at somewhat higher doses in the treatment of congestive heart failure. The principal pharmacological action of nitroglycerin is relaxation of vascular smooth muscle, so as to produce a vasodilator effect on both peripheral arteries and veins.
Nitroglycerin was originally administered orally and, later, bucally. More recently, transdermal systems have been developed which have been found to improve the systemic bioavailability of the drug. The Nitro-Dur.RTM. Transdermal Infusion System manufactured and sold by Key Pharmaceuticals, Inc. (Kenilworth, N.J.), the Nitrodisc.RTM. made by Searle Pharmaceuticals, Inc. (Chicago, Ill.), the Nitroglycerin Transdermal System of Bolar Pharmaceutical Co., Inc. (Copiague, N.Y.), the Transderm-Nitro.RTM. system distributed by CIBA Pharmaceutical Co. (Summit, N.J.), and the Minitran.RTM. system of Riker Pharmaceuticals (St. Paul, Minn.) are examples of the currently available transdermal nitroglycerin systems.
Several problems which have been encountered with the transdermal administration of nitroglycerin include the tolerance to the drug which results from prolonged administration. Higher and higher doses are required for patients on long-term nitroglycerin therapy, necessitating the use of larger and larger transdermal patches. This is obviously inconvenient and undesirable. Accordingly, the present invention is directed to a method and system for administering nitroglycerin transdermally, and provides for a relatively high transdermal flux using a more conveniently sized, smaller patch. The invention may also be useful to treat indications other than angina pectoris, e.g., congestive heart failure or production of controlled hypotension during surgery and perioperative to surgery, which require higher doses of nitroglycerin. The invention involves the transdermal administration of nitroglycerin in combination with a low irritation skin permeation enhancer--either a sorbitan ester, a C.sub.8 -C.sub.22 aliphatic alcohol, or a mixture thereof.